scholarly journals Development and Characterization of a Guinea Pig-Adapted Sudan Virus

2015 ◽  
Vol 90 (1) ◽  
pp. 392-399 ◽  
Author(s):  
Gary Wong ◽  
Shihua He ◽  
Haiyan Wei ◽  
Andrea Kroeker ◽  
Jonathan Audet ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Lethal Dose ◽  
Fatal Outcome ◽  
Small Animal ◽  
Disease Outbreak ◽  
Small Animal Model ◽  
Content Type

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.

scholarly journals Pathology and Pathophysiology of Inhalational Anthrax in a Guinea Pig Model

2013 ◽  
Vol 81 (4) ◽  
pp. 1152-1163 ◽  
Author(s):  
Vladimir Savransky ◽  
Daniel C. Sanford ◽  
Emily Syar ◽  
Jamie L. Austin ◽  
Kevin P. Tordoff ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pig ◽  
Lymph Nodes ◽  
Guinea Pigs ◽  
Alternative Model ◽  
Lethal Dose ◽  
Clinical Signs ◽  
Regional Lymph Nodes ◽  
Content Type ◽  
Ames Strain

ABSTRACTNonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's “Animal Rule.” However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD50) of theBacillus anthracisAmes strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD50of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 104spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans.

scholarly journals Effects of an antiplatelet glycoprotein Ib antibody on hemostatic function in the guinea pig

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 690-694 ◽  
Author(s):  
BH Becker ◽  
JL Miller
Keyword(s):  
Animal Model ◽  
Platelet Count ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Bleeding Time ◽  
Model System ◽  
Platelet Counts ◽  
Equal Dose ◽  
Guinea Pig Model

Abstract Previous studies in the guinea pig model system have established a close structural homology between human and guinea pig glycoproteins Ib (GPIb) and IIb/IIIa (GPIIb/IIIa). Moreover, the murine monoclonal antibody (MoAb) PG-1, which recognizes GPIb in guinea pig platelets and megakaryocytes, exerted full inhibition on von Willebrand factor (vWF)- dependent platelet agglutination without inhibiting aggregation induced by ADP, collagen, or thrombin. The present research extends this animal model system to study of the effects on hemostatic function following the in vivo injection of MoAb PG-1 or its F(ab')2 fragments. A hind limb template bleeding time methodology was developed for use in guinea pigs. Normal bleeding time was determined to be 2.7 +/- 0.5 minutes (mean +/- SD), with an observed range of two to four minutes. Platelet counts in these same animals were 501 +/- 82 x 10(3)/microL. After intraperitoneal (IP) injection of busulfan, guinea pigs became increasingly thrombocytopenic. As long as the platelet count remained above approximately 150 x 10(3)/microL, the bleeding time was not more than five minutes; however, further decrease in the platelet count was accompanied by more marked prolongations of the bleeding time. For 14 to 72 hours after IP injection of 1.3 mg/kg intact PG-1 MoAb, a hemorrhagic state was produced with a bleeding time greater than 20 minutes. The platelet count concurrently decreased to approximately 50% of its baseline value but could not be further decreased either by raising the initial PG-1 dosage tenfold or by administering a second, equal dose 24 hours after the initial injection. This finding may reflect a heterogeneity of circulating platelets with respect to GPIb, to Fc receptors, or to an interaction between them. After IP injection of 0.63 to 2.5 mg/kg PG-1 F(ab')2 fragment, platelet counts did not decrease more than 21% below baseline levels in a 72-hour period, and bleeding times never increased by more than one minute over baseline values. Nevertheless, platelets obtained from animals 24 hours after injection of 2.5 mg/kg PG-1 F(ab')2 showed full inhibition of agglutination induced by ristocetin. The response of these platelets to aggregation by asialo-vWF was also severely inhibited as compared with control platelets. PG-1 F(ab')2 produced no effect on aggregation induced by ADP. These studies show that virtually complete functional block of the vWF receptor by F(ab')2 fragments of the anti-GPIb MoAb PG- 1 is not sufficient to produce a hemorrhagic state in the guinea pig animal model system.

The pre-term guinea-pig: a model for the study of neonatal lung disease

1991 ◽  
Vol 81 (3) ◽  
pp. 439-446 ◽  
Author(s):  
F. J. Kelly ◽  
G. I. Town ◽  
G. J. Phillips ◽  
S. T. Holgate ◽  
W. R. Roche ◽  
...  
Keyword(s):  
Animal Model ◽  
Lung Injury ◽  
Guinea Pig ◽  
Bronchoalveolar Lavage ◽  
Lung Disease ◽  
Bronchoalveolar Lavage Fluid ◽  
Small Animal ◽  
Lavage Fluid ◽  
Small Animal Model ◽  
Neonatal Lung

1. Research into the pathogenesis of acute and chronic neonatal lung disease has been hampered by the lack of a suitable small-animal model of prematurity. We describe such a model that has been developed and validated in the guinea-pig. 2. Pre-term guinea-pigs delivered by Caesarian section at 65 days gestation (normal gestation 68 days) exhibited transient respiratory distress. The survival of pre-term animals was lower than that of term animals after exposure to 95% O2 (pre-term 42% versus term 79% at 96 h, P < 0.05). 3. Pulmonary histology in pre-term animals exposed to both 21% O2 and 95% O2 revealed evidence of acute lung injury with atelectasis, pulmonary oedema, fibrin deposition and inflammatory cell infiltration. No evidence of lung injury was observed in term animals exposed to 21% O2, whereas those exposed to 95% O2 showed a similar, but less pronounced, injury to that seen in preterm pups. 4. The protein concentration in bronchoalveolar lavage fluid was similar in pre-term and term animals exposed to 95% O2, but neutrophil numbers in bronchoalveolar lavage fluid tended to be greater in preterm pups. 5. Elastase-like activity, measured against succinyl-1-trialanine p-nitroanilide, was higher in bronchoalveolar lavage fluid from control pre-term animals compared with that from control term animals. Exposure to 95% O2 increased the elastase-like activity significantly in both groups. The majority of the elastase-like activity was EDTA-sensitive and thus is possibly due to metallo-elastase. Fractionation of bronchoalveolar lavage fluid indicated that the elastase-like activity was associated with a high-molecular-mass complex. Lipase treatment reduced the activity of this fraction and generated a new 40 kDa fraction. 6. We conclude that the pre-term guinea-pig is more susceptible than the term animal to lung injury after O2 exposure and thus represents a appropriate small-animal model in which to investigate the pathogenesis of acute and chronic lung injury in the pre-term infant.

scholarly journals IMMUNOLOGY OF THE PERUVIAN STRAINS OF LEPTOSPIRA ICTEROIDES

1921 ◽  
Vol 33 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler
Keyword(s):  
New York ◽  
Guinea Pig ◽  
Incubation Period ◽  
Yellow Fever ◽  
Guinea Pigs ◽  
Lethal Dose ◽  
Fatal Outcome ◽  
Rabbit Serum ◽  
Minimum Lethal Dose ◽  
Lethal Doses

Serum from yellow fever convalescents from Payta, Piura, and Morropon gave a positive Pfeiffer reaction with the strains of Leptospira icteroides isolated in Guayaquil and Merida. The serum also protected the guinea pigs from these strains in the majority of instances. The Pfeiffer reaction was complete with all recent convalescents (7 to 36 days) but slight or partial in some instances with serum derived from individuals who had had the attack of yellow fever 10 months previously. The virulence of the Morropon strains was found to be approximately the same as that of the Guayaquil or Merida strains. With one strain the minimum lethal dose for the guinea pig was less than 0.00001 cc. of a kidney emulsion from an infected guinea pig. Suitable quantities of the anti-icteroides serum administered to guinea pigs inoculated with 2,000 to 20,000 minimum lethal doses of infective material prevented the development of the infection, or a fatal outcome, according as the serum was given during the incubation period or after fever had appeared. The earlier the administration of the serum the smaller was the quantity needed; during the incubation period 0.0001 to 0.001 cc. was sufficient, during the febrile period 0.01 to 0.1 cc. was required to check the progress of the disease, and even at the time when jaundice had already appeared, the injection of 0.1 to 1 cc. saved three out of four animals inoculated with Strain 3 and one out of three inoculated with Strain 1. The native guinea pigs secured in Payta proved to be unusually refractory to infection with Leptospira icteroides as compared with normal guinea pigs recently imported from New York. Fresh rabbit serum is recommended for culture work with Leptospira icteroides.

scholarly journals The ascorbate-deficient guinea pig model of shigellosis allows the study of the entire Shigella life cycle

2020 ◽  
Author(s):  
Antonin C André ◽  
Céline Mulet ◽  
Mark C Anderson ◽  
Louise Injarabian ◽  
Achim Buch ◽  
...  
Keyword(s):  
Animal Model ◽  
Life Cycle ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Colonic Mucosa ◽  
Extended Period ◽  
Pig Model ◽  
Suitable Animal Model ◽  
Guinea Pig Model

AbstractShigella spp. are the causative agents of bacillary dysentery or shigellosis, mainly in children living in developing countries. The study of Shigella entire life cycle in vivo and the evaluation of vaccine candidates’ protection efficacy have been hampered by the lack of a suitable animal model of infection (1). None of the ones evaluated so far (mouse, rabbit, guinea pig) allows to recapitulate shigellosis symptoms upon Shigella oral challenge. Historical reports suggest that dysentery and scurvy are both metabolic diseases associated with ascorbate-deficiency. Mammals which are susceptible to Shigella infection (humans, non-human primates and guinea pigs) are the lonely ones which are unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate-deficiency but not scurvy in guinea pigs (Ascplasma conc.=1.6 μM vs 36 μM with optimal ascorbate supply). We demonstrated that moderate ascorbate-deficiency increases shigellosis severity during extended period of time (up to 48h) with all strains tested (Shigella flexneri 5a and 2a, Shigella sonnei). At late time-points, a massive influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although Shigella remains able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. This new model of shigellosis opens new doors for the study both of Shigella infection strategy and innate and adaptive immune responses to Shigella infection. It may be also of a great interest to study the virulence of other pathogen for which no suitable animal model of infection is available (Vibrio cholerae, Yersinia pestis, Mycobacterium tuberculosis or Campylobacter jejuni, among others).SignificanceThe study of Shigella virulence cycle in vivo has been hampered by the lack of a suitable animal model, which would allow the colonic mucosa infection upon oral challenge. Based on historical reports and physiological aspects, it was suggested that ascorbate-deficiency may stand as a new dysentery risk-factor. To test this hypothesis, we set up a new ascorbate-deficient guinea pig model and demonstrated for the first time that the Shigella infectious process occurred for extended period of time (up to 48h) and demonstrated that shigellosis severity was higher in ascorbate-deficient animal. Ascorbate-deficient guinea pig model of infection may be used to assess the virulence of other pathogens for which no suitable animal model of infection is still lacking.

A model of brain abscess: septic homologous blood clot emboli in rats

1986 ◽  
Vol 64 (1) ◽  
pp. 125-127 ◽  
Author(s):  
Hiroshi Matsuura ◽  
Motoshige Kudo ◽  
Yukio Ikeda ◽  
Kazuo Isayama ◽  
Shozo Nakazawa
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Blood Clot ◽  
Small Animal ◽  
Small Animal Model ◽  
Homologous Blood ◽  
Content Type ◽  
Therapeutic Procedures ◽  
Brain Abscesses ◽  
Fine Print

✓ Brain abscesses in rats were produced by intra-arterial injection of septic homologous blood clot emboli. The production rate was 100% and the histopathological features closely resembled those seen in other animal models and in spontaneously occurring brain abscesses in humans. This small-animal model may be useful for systematic study of the development of brain abscesses as well as for evaluation of various therapeutic procedures.

Intrathecal Catheterization and Drug Delivery in Guinea Pigs

2016 ◽  
Vol 125 (2) ◽  
pp. 378-394 ◽  
Author(s):  
Kelly A. Eddinger ◽  
Eric S. Rondon ◽  
Veronica I. Shubayev ◽  
Marjorie R. Grafe ◽  
Miriam Scadeng ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pigs ◽  
Ex Vivo ◽  
Intrathecal Morphine ◽  
Small Animal ◽  
Thermal Stimulus ◽  
Small Animal Model ◽  
Morphine Infusion ◽  
Catheter Tip ◽  
Intrathecal Infusion

Abstract Background Intrathecal infusion of opioids in dogs, sheep, and humans produces local space-occupying masses. To develop a small-animal model, the authors examined effects of intrathecal catheterization and morphine infusion in guinea pigs. Methods Under isoflurane, polyethylene or polyurethane catheters were advanced from the cisterna magna to the lumbar enlargement. Drugs were delivered as a bolus through the externalized catheter or continuously by subcutaneous minipumps. Hind paw withdrawal to a thermal stimulus was assessed. Spinal histopathology was systematically assessed in a blinded fashion. To assist in determining catheter placement, ex vivo images were obtained using magnetic resonance imaging in several animals. Canine spinal tissue from previous intrathecal morphine studies was analyzed in parallel. Results (1) Polyethylene (n = 30) and polyurethane (n = 25) catheters were implanted in the lumbar intrathecal space. (2) Bolus intrathecal morphine produced a dose-dependent (20 to 40 μg/10 μl) increase in thermal escape latencies. (3) Absent infusion, a catheter-associated distortion of the spinal cord and a fibrotic investment were noted along the catheter tract (polyethylene &gt; polyurethane). (4) Intrathecal morphine infusion (25 mg/ml/0.5 μl/h for 14 days) resulted in intrathecal masses (fibroblasts, interspersed collagen, lymphocytes, and macrophages) arising from meninges proximal to the catheter tip in both polyethylene- and polyurethane-catheterized animals. This closely resembles mass histopathology from intrathecal morphine canine studies. Conclusions Continuous intrathecal infusion of morphine leads to pericatheter masses that morphologically resemble those observed in dogs and humans. This small-animal model may be useful for studying spinal drug toxicology in general and the biology of intrathecal granuloma formation in particular.

scholarly journals Ferrets Infected with Bundibugyo Virus or Ebola Virus Recapitulate Important Aspects of Human Filovirus Disease

2016 ◽  
Vol 90 (20) ◽  
pp. 9209-9223 ◽  
Author(s):  
Robert Kozak ◽  
Shihua He ◽  
Andrea Kroeker ◽  
Marc-Antoine de La Vega ◽  
Jonathan Audet ◽  
...  
Keyword(s):  
Animal Model ◽  
Ebola Virus ◽  
Virus Transmission ◽  
Case Fatality ◽  
Small Animal ◽  
Hemorrhagic Fever ◽  
Transmission Model ◽  
Global Public Health ◽  
Small Animal Model ◽  
Content Type

ABSTRACTBundibugyo virus (BDBV) is the etiological agent of a severe hemorrhagic fever in humans with a case-fatality rate ranging from 25 to 36%. Despite having been known to the scientific and medical communities for almost 1 decade, there is a dearth of studies on this pathogen due to the lack of a small animal model. Domestic ferrets are commonly used to study other RNA viruses, including members of the orderMononegavirales. To investigate whether ferrets were susceptible to filovirus infections, ferrets were challenged with a clinical isolate of BDBV. Animals became viremic within 4 days and succumbed to infection between 8 and 9 days, and a petechial rash was observed with moribund ferrets. Furthermore, several hallmarks of human filoviral disease were recapitulated in the ferret model, including substantial decreases in lymphocyte and platelet counts and dysregulation of key biochemical markers related to hepatic/renal function, as well as coagulation abnormalities. Virological, histopathological, and immunohistochemical analyses confirmed uncontrolled BDBV replication in the major organs. Ferrets were also infected with Ebola virus (EBOV) to confirm their susceptibility to another filovirus species and to potentially establish a virus transmission model. Similar to what was seen with BDBV, important hallmarks of human filoviral disease were observed in EBOV-infected ferrets. This study demonstrates the potential of this small animal model for studying BDBV and EBOV using wild-type isolates and will accelerate efforts to understand filovirus pathogenesis and transmission as well as the development of specific vaccines and antivirals.IMPORTANCEThe 2013-2016 outbreak of Ebola virus in West Africa has highlighted the threat posed by filoviruses to global public health. Bundibugyo virus (BDBV) is a member of the genusEbolavirusand has caused outbreaks in the past but is relatively understudied, likely due to the lack of a suitable small animal model. Such a model for BDBV is crucial to evaluating vaccines and therapies and potentially understanding transmission. To address this, we demonstrated that ferrets are susceptible models to BDBV infection as well as to Ebola virus infection and that no virus adaptation is required. Moreover, these animals develop a disease that is similar to that seen in humans and nonhuman primates. We believe that this will improve the ability to study BDBV and provide a platform to test vaccines and therapeutics.

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